Eeffects And Mechanisms Of Shenkang Injection Improving Renal Interstitial Fibrosis By Regulating Pericyte-myofibroblast Transition

[Background/Aims]This study is made up of two parts.In the fIrst part,the authors reviewed the pathomechanisms of pericyte-myofibroblast transition(PMT)and the interventional effects of Chinese herbal medicine(CHM).The pathological characters of renal interstitial fibrosis(RIF)include tubular atrophy,extracellular matrix(ECM)accumulation,inflammatory cell infiltration and myofibroblast(MyoF)proliferation in renal interstitium.The regulatory mechanism of PMT is closely related to the activation of multiple signaling pathways,such as transforming growth factor(TGF)-? pathway,vascular endothelial growth factor receptor(VEGFR)pathway and platelet derived growth factor receptor(PDGFR)pathway.RIF can be improved in the different ways through some Chinese herbal compound or single CHM extracts such as multi-glycoside of Tripterygium wilfordii Hook.f.,puerarin and Jiawei Buyang Huanwu Decoction In the second part,as the focus of this study,using the unilateral ureteral obstruction(UUO)model rats,the authors aimed to clarify the effects and mechanisms of shenkang injection(SKI)improving RIF in vivo.[Methods]The RIF model was induced by UUO.The 25 rats were randomly divided into 5 groups,the sham-operated(Sham)group,the model(Model)group,the high dose of SKI(H-SKI)group,the low dose of SKI(L-SKI)groiup and the imatinib(IMA)group(5 rats for each group).The rats in H-SKI,L-SKI and IMA groups were given daily H-SKI(5 g-kg-1),L-SKI(1 g-kg-1)and IMA(50 mg-kg1-1)respectively by the intraperitoneal injection,while the rats in Sham and Model groups were given daily respectively the double distilled water(2 mL)through the intragastric administration.The rats were given drugs before and after modeling for 2 weeks,and sacrificed at 4 weeks after the drug administration.And that,their urine/hydronephrosis,blood and kidneys were collected and examined respectively,and then investigated the effects of SKI on indicators of efficacy,the protein expressions of pericyte and MyoF markers and the related indicators of VEGFR and PDGFR signaling pathways.[Results]For the UUO model rats,both SKI and IMA could improve kidney appearance and urinary N-acetyl-p-D-glucosaminidase(UNAG);Both of them could ameliorate renal interstitial morphology,reduce ECM accumulation and collagen deposition,moreover,the effects of H-SKI were better than L-SKI and IMA;SKI could improve the pericyte micromorphological characters;Both of them could down-regulate the protein expressions of pericyte and MyoF markers,moreover,the effects of H-SKI were better than L-SKI and IMA;Both SKI and IMA could improve the protein expressions of the key signaling molecules of VEGFR and PDGFR signaling pathways in the kidney in different extent;Nevertheless,neither SKI nor IMA had the effects on body weight(BW),kidney weight(KW),renal function and serum albumin(Alb).[Conclusion]By means of the UUO model rats,the authors demonstrated that? Both SKI and IMA can improve RIF,and that the effects of H-SKI are better than IMA;?Both SKI and IMA can regulate the protein expressions of PMT markers in renal interstitium,and that,the effects of H-SKI are better than IMA;?Both SKI and IMA can inhibit the activation of VEGFR and PDGFR signaling pathways.